Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex
Sirolimus is already used in the treatment of tuberous sclerosis complex (TSC), however, with narrow therapeutic range and considerable inter- and intra-individual pharmacokinetic variability, making it hard to develop an appropriate sirolimus initial dosage regimen, especially in children with TSC....
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00890/full |
| _version_ | 1818131402115252224 |
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| author | Dong-Dong Wang Xiao Chen Hong Xu Zhi-Ping Li |
| author_facet | Dong-Dong Wang Xiao Chen Hong Xu Zhi-Ping Li |
| author_sort | Dong-Dong Wang |
| collection | DOAJ |
| description | Sirolimus is already used in the treatment of tuberous sclerosis complex (TSC), however, with narrow therapeutic range and considerable inter- and intra-individual pharmacokinetic variability, making it hard to develop an appropriate sirolimus initial dosage regimen, especially in children with TSC. The aim of this study was to recommend the optimal sirolimus initial dosing regimen in pediatric patients with TSC. Underlying physiological and genetic factors were collected to explore the effects on clinical sirolimus concentrations by establishing a nonlinear mixed effect (NONMEM) model, and to further simulate the optimal sirolimus initial dosing regimen using Monte Carlo method in pediatric patients with TSC. The once-daily regimen and the twice-daily regimen were recommended, respectively. For once-daily regimen, the dosages of 0.10, 0.07, 0.05, 0.04, 0.03 mg/kg/day were recommended for children with weights of 5–10, 10–20, 20–30, 30–50, and 50–60 kg, respectively. For twice-daily regimen, the dosages of 0.04, 0.03, 0.02 mg/kg/day (the daily dose was divided evenly into two doses) were recommended for children with weights of 5–20, 20–40, 40–60 kg, respectively. The initial dosages of sirolimus in children with TSC were recommended for the first time. |
| first_indexed | 2024-12-11T08:20:22Z |
| format | Article |
| id | doaj.art-d0f8796821d2498db67e807d9fd8fbfa |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T08:20:22Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d0f8796821d2498db67e807d9fd8fbfa2022-12-22T01:14:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00890536678Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis ComplexDong-Dong Wang0Xiao Chen1Hong Xu2Zhi-Ping Li3Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Pharmacy, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Pharmacy, Children's Hospital of Fudan University, Shanghai, ChinaSirolimus is already used in the treatment of tuberous sclerosis complex (TSC), however, with narrow therapeutic range and considerable inter- and intra-individual pharmacokinetic variability, making it hard to develop an appropriate sirolimus initial dosage regimen, especially in children with TSC. The aim of this study was to recommend the optimal sirolimus initial dosing regimen in pediatric patients with TSC. Underlying physiological and genetic factors were collected to explore the effects on clinical sirolimus concentrations by establishing a nonlinear mixed effect (NONMEM) model, and to further simulate the optimal sirolimus initial dosing regimen using Monte Carlo method in pediatric patients with TSC. The once-daily regimen and the twice-daily regimen were recommended, respectively. For once-daily regimen, the dosages of 0.10, 0.07, 0.05, 0.04, 0.03 mg/kg/day were recommended for children with weights of 5–10, 10–20, 20–30, 30–50, and 50–60 kg, respectively. For twice-daily regimen, the dosages of 0.04, 0.03, 0.02 mg/kg/day (the daily dose was divided evenly into two doses) were recommended for children with weights of 5–20, 20–40, 40–60 kg, respectively. The initial dosages of sirolimus in children with TSC were recommended for the first time.https://www.frontiersin.org/article/10.3389/fphar.2020.00890/fullinitial dosagerecommendationsirolimuschildrentuberous sclerosis complex |
| spellingShingle | Dong-Dong Wang Xiao Chen Hong Xu Zhi-Ping Li Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex Frontiers in Pharmacology initial dosage recommendation sirolimus children tuberous sclerosis complex |
| title | Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex |
| title_full | Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex |
| title_fullStr | Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex |
| title_full_unstemmed | Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex |
| title_short | Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex |
| title_sort | initial dosage recommendation for sirolimus in children with tuberous sclerosis complex |
| topic | initial dosage recommendation sirolimus children tuberous sclerosis complex |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00890/full |
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